The present invention relates to antibiotic compounds and in particular to antibiotic compounds containing an oxazolidinone ring. This invention further relates to processes for their preparation, to intermediates useful in their preparation, to their use as therapeutic agents and to pharmaceutical compositions containing them.
The international microbiological community continues to express serious concern that the evolution of antibiotic resistance could result in strains against which currently available antibacterial agents will be ineffective. In general, bacterial pathogens may be classified as either Gram-positive or Gram-negative pathogens. Antibiotic compounds with effective activity against both Gram-positive and Gram-negative pathogens are generally regarded as having a broad spectrum of activity. The compounds of the present invention are regarded primarily as effective against Gram-positive pathogens because of their particularly good activity against such pathogens.
Gram-positive pathogens, for example Staphylococci, Enterococci. Streptococci and mycobacteria, are particularly important because of the development of resistant strains which are both difficult to treat and difficult to eradicate from the hospital environment once established. Examples of such strains are methicillin resistant staphylococcus (MRSA). methicillin resistant coagulase negative staphylococci (MRCNS), penicillin resistant streptococcus pneumoniae and multiply resistant Enterococcus faecium. 
The major clinically effective antibiotic for treatment of such resistant Gram-positive pathogens is vancomycin. Vancomycin is a glycopeptide and is associated with nephrotoxicity and ototoxicity. Furthermore, and most importantly, antibacterial resistance to vancomycin and other glycopeptides is also appearing. This resistance is increasing at a steady rate rendering these agents less and less effective in the treatment of Gram-positive pathogens.
The present inventor has discovered a class of antibiotic compounds containing an oxazolidinone ring which has useful activity against Gram-positive pathogens including MRSA and MRCNS and, in particular, against various strains exhibiting resistance to vancomycin and against E. faecium strains resistant to both aminoglycosides and clinically used xcex2-lactams.
We have now discovered a narrow range of compounds that is not suggested by the art and which has good activity against a broad range of Gram-positive pathogens including organisms known to be resistant to most commonly used antibiotics. In comparison with compounds described in the art (Walter A. Gregory et al in J.Med.Chem. 1990, 33, 2569-2578 and Chung-Ho Park et al in J.Med.Chem. 1992, 35, 1156-1165) the compounds also possess a favourable toxicological profile.
Accordingly the present invention provides a compound of the formula (I): 
wherein:
T is of the formula (IA), (IB) or (IC); 
(wherein the R6 group in (IC) may be in the 2- or 6-position relative to the ring nitrogen atom);
R1 is chloro, fluoro, (1-4C)alkanesulfonyloxy, azido, (1-4C)alkoxy, (1-4C)alkylthio, (1-4C)alkylaminocarbonyloxy;
or of the formula xe2x80x94NHC(xe2x95x90O)Rb wherein Rb is hydrogen, (1-4C)alkoxy, amino, chloromethyl, dichloromethyl, cyanomethyl, methoxymethyl, acetylmethyl, methylamino, dimethylamino or (1-4C)alkyl; or of the formula xe2x80x94NHS(O)n(1-4C)alkyl wherein n is 0, 1 or 2;
R2 and R3 are independently hydrogen or fluoro;
 greater than Axe2x80x94Bxe2x80x94 is  greater than Cxe2x95x90CHxe2x80x94,  greater than C(R4)xe2x80x94CH2xe2x80x94,  greater than CHxe2x80x94CH2xe2x80x94,  greater than Cxe2x95x90C(R4a)xe2x80x94,  greater than C(R4)xe2x80x94, CH(R4a)xe2x80x94 or
 greater than CHxe2x80x94CH(R4a)xe2x80x94(wherein, herein and hereinafter,  greater than represents two single bonds), provided that  greater than Axe2x80x94Bxe2x80x94 is not  greater than Cxe2x95x90CHxe2x80x94,  greater than Cxe2x95x90C(R4a)xe2x80x94,  greater than C(R4)xe2x80x94 or  greater than CHxe2x80x94CH(R4a)xe2x80x94 when T is of the formula (IA); wherein R4 is hydrogen, hydroxy, halo, (1-4C)alkyl or (1-4C)alkanoyloxy;
R4a is (1-4C)alkyl; m is 0 or 1;
wherein when T is of the formula (IA) or (IB);
R6 is (1-4C)alkyl, (1-4C)alkanoylamino-(1-4C)alkyl, hydroxy-(1-4C)alkyl, carboxy, (1-4C)alkoxycarbonyl, AR-oxymethyl, AR-thiomethyl (wherein AR is as defined hereinbelow) or independently as defined for R5 hereinbelow (excluding R5 as hydrogen);
R5 is hydrogen, cyano, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, trityl or AR (as defined hereinbelow);
or R5 is of the formula R10COxe2x80x94, R10SO2xe2x80x94 or R10CSxe2x80x94 wherein R10 is AR (as defined hereinbelow), cyclopentyl or cyclohexyl (wherein the last two-mentioned cycloalkyl rings are optionally mono- or disubstituted by substituents independently selected from (1-4C)alkyl (including geminal disubstitution), hydroxy, (1-4C)alkoxy, (1-4C)alkylthio, acetamido, (1-4C)alkanoyl, cyano and trifluoromethyl), benzyloxy, (1-4C)alkoxycarbonyl, hydrogen, amino, trifluoromethyl, (1-4C)alkylamino, di((1-4C)alkyl)amino, 2-(2-furyl)ethenyl, 2-(2-thienyl)ethenyl, 2-phenylethenyl (wherein the phenyl substituent is optionally substituted by up to three substituents independently selected from (1-4C)alkoxy halo and cyano), benzopyranone or (1-10C)alkyl [wherein (1-10C)alkyl is optionally substituted by hydroxy, benzyloxy, cyano, halo, (1-10C)alkoxy, trifluoromethyl, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkanoyl, (1-4C)alkoxycarbonyl, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(2-6C)alkanoylamino, (1-4C)alkylS(O)pNHxe2x80x94, (1-4C)alkylS(O)p((1-4C)alkyl)Nxe2x80x94, fluoro(1-4C)alkylS(O)pNHxe2x80x94, fluoro(1-4C)alkylS(O)p((1-4C)alkyl)Nxe2x80x94, phosphono, (1-4C)alkoxy(hydroxy)phosphoryl, di-(1-4C)alkoxyphosphoryl, (1-4C)alkylS(O)qxe2x80x94, phenylS(O)qxe2x80x94(wherein the phenyl group is optionally substituted by up to three substituents independently selected from (1-4C)alkoxy, halo and cyano), or CY (as defined hereinbelow), wherein p is 1 or 2 and q is 0, 1 or 2];
or R10 of the formula R11C(O)O(1-6C)alkyl wherein R11 is an optionally substituted 5- or 6-membered heteroaryl, optionally substituted phenyl, (1-4C)alkylamino, benzyloxy-(1-4C)alkyl or optionally substituted (1-10C)alkyl,
or R10 is of the formula R12Oxe2x80x94 wherein R12 is optionally substituted (1-6C)alkyl;
or R5 is of the formula Rd OC(Rc)xe2x95x90CH(Cxe2x95x90O)xe2x80x94, RfC(xe2x95x90O)C(xe2x95x90O)xe2x80x94, RgNxe2x95x90C(Rh)C(xe2x95x90O)xe2x80x94 or RiNHC(Rj)xe2x95x90CHC(xe2x95x90O)xe2x80x94 wherein Rd is (1-6C)alkyl, Re is hydrogen or (1-6C)alkyl, or Rd and Re together form a (3-4C)alkylene chain, Rf is hydrogen, (1-6C)alkyl, hydroxy(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-6C)alkoxy, (1-6C)alkoxy(1-6C)alkoxy, hydroxy(2-6C)alkoxy, (1-4C)alkylamino(2-6C)alkoxy), di-(1-4C)alkylamino(2-6C)alkoxy, Rg is (1-6C)alkyl, hydroxy or (1-6C)alkoxy, Rh is hydrogen or (1-6C)alkyl, Ri is hydrogen, (1-6C)alkyl, optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl and Rj is hydrogen or (1-6C)alkyl;
or R5 is of the formula R14CH(R13)(CH2)mxe2x80x94 wherein m is 0 or 1, R13 is fluoro, cyano, (1-4C)alkoxy, (1-4C)alkylsulfonyl, (1-4C)alkoxycarbonyl or hydroxy, (provided that when m is 0, R13 is not fluoro or hydroxy) and R14 is hydrogen or (1-4C)alkyl;
or when T is of the formula (IA), (IB) or (IC) R5 is ethenyl, 2-(AR)ethenyl, 2-(1-4C)alkylethenyl or of the formula (ID) 
wherein X is xe2x80x94OR15, xe2x80x94SR15, xe2x80x94NHR15 and xe2x80x94N(R15)2 wherein R15 is hydrogen (when X is xe2x80x94NHR15 and xe2x80x94N(R15)2), (1-4C)alkyl or AR (as defined hereinbelow, when X is xe2x80x94OR15, xe2x80x94SR15 and xe2x80x94NHR15); and R16 is cyano, nitro, (1-4C)alkylsulfonyl, (4-10C)cycloalkylsulfonyl, phenylsulfonyl, (1-4C)alkanoyl and (1-4C)alkoxycarbonyl;
or when T is of the formula (IA), (IB) or (IC);
R5 and R6 are linked to give a group of the formula (IE) to (IT) [in which the N-atom shown is linked to R5 in (IA) to (IC), and the adjacent carbon atom shown in (IE) to (IT) is linked to R6 in (IA) to (IC)] so that a 5- or 6-membered ring is formed which is fused to the ring shown in (IA), (IB) or (IC) so as to give a bicyclic ring structure: 
xe2x80x83wherein
D is independently selected from  greater than C(R7)(R8) [or xe2x95x90C(R8)xe2x80x94 when D is connected to a carbon-carbon double bond, wherein xe2x95x90 represents a carbon-carbon double bond], S(O)p [wherein p is 0, 1 or 2] and xe2x80x94Oxe2x80x94 [when D is not connected to a carbon-carbon double bond] and xe2x80x94NR9 [or N when D is connected to a carbon-carbon double bond);
E is independently selected from  greater than C(R7)(R8) [or xe2x95x90C(R8)xe2x80x94 when E is connected to a carbon-carbon double bond], S(O)p [wherein p is 0, 1 or 2] and  greater than Cxe2x95x90O [when E is not connected to a carbon-carbon double bond];
wherein R7 and R8 are independently selected from hydrogen, (1-4C)alkyl, (optionally substituted by hydroxy, trifluoromethyl, (1-4C)alkyl S(O)qxe2x80x94 (wherein q is 0, 1 or 2), (1-4C)alkoxy, carboxy, (1-4C)alkoxycarbonyl, carbamoyl, N-(1-4C)alkylcarbamoyl, di(N-(1-4C)alkyl)carbamoyl, cyano, nitro, amino, N-(1-4C)alkylamino,
di(N-(1-4C)alkyl)amino or (1-4C)alkanoylamino), hydroxy [when D and E are not connected to a carbon-carbon double bond], (1-4C)alkoxy, halo, trifluoromethyl, thiol, (1-4C)alkylS(O)q (wherein q is 0, 1 or 2), carboxy, (1-4C)alkoxycarbonyl, (1-4C)alkanoyl, carbamoyl, N-(1-4C)alkylcarbamoyl, di(N-(1-4C)alkyl)carbamoyl, (2-4C)alkenyl (optionally substituted by carboxy or (1-4C)alkoxycarbonyl), cyano, (1-4C)alkanoylamino, amino, N-(1-4C)alkylamino, di(N-(1-4C)alkyl)amino or nitro;
wherein R9 is hydrogen, AR, trifluoromethyl, hydroxy, cyano, ethenyl), 2-(AR)ethenyl, 2-(1-4C)alkylethenyl, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, benzopyranone or (1-10C)alkyl [wherein (1-10C)alkyl is optionally substituted by hydroxy, halo (provided that (1-10C)alkyl is not methyl when substituted by hydroxy or halo), cyano,(1-10C)alkoxy, trifluoromethyl, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkanoyl, (1-4C)alkoxycarbonyl, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(2-6C)alkanoylamino, (1-4C)alkylS(O)pNHxe2x80x94, (1-4C)alkylS(O)p((1-4C)alkyl)Nxe2x80x94, fluoro(1-4C)alkylS(O)pNHxe2x80x94, fluoro(1-4C)alkylS(O)p((1-4C)alkyl)Nxe2x80x94, phosphono, (1-4C)alkoxy(hydroxy)phosphoryl, di-(1-4C)alkoxyphosphoryl, (1-4C)alkylS(O)qxe2x80x94, phenylS(O)qxe2x80x94(wherein the phenyl group is optionally substituted by up to three substituents independently selected from (1-4C)alkoxy, halo and cyano), AR or CY (as defined hereinbelow), wherein p is 1 or 2 and q is 0, 1 or 2];
or R9 is of the formula R11C(O)O(1-6C)alkyl wherein R11 is an optionally substituted 5- or 6-membered heteroaryl, optionally substituted phenyl, (1-4C)alkylamino. benzyloxy-(1-4C)alkyl or optionally substituted (1-10C)alkyl;
or R9 is of the formula R12Oxe2x80x94 wherein R12 is optionally substituted (1-6C)alkyl;
wherein AR is optionally substituted phenyl, phenylcarbonyl (when in AR-oxymethyl), optionally substituted phenyl(1-4C)alkyl, optionally substituted 5- or 6-membered heteroaryl, optionally substituted naphthyl or an optionally substituted 5/6 or 6/6 bicyclic heteroaryl ring system, in which the bicyclic heteroaryl ring systems may be linked via an atom in either of the rings comprising the bicyclic system, and wherein the mono- and bicyclic heteroaryl ring systems are linked via a ring carbon atom;
wherein CY is a 4-, 5- or 6-membered cycloalkyl ring, or a 5- or 6-membered cycloalkenyl ring; wherein any of the afore-mentioned ring systems in CY may be optionally substituted by up to three substituents independently selected from halo, (1-4C)alkyl (including geminal disubstitution when CY is a cycloalkyl or cycloalkenyl ring), acyl, oxo and nitro-(1-4C)alkyl;
or a pharmaceutically-acceptable salt thereof
In this specification a xe2x80x985- or 6-membered heteroarylxe2x80x99 and xe2x80x98heteroaryl (monocyclic) ringxe2x80x99 means a 5- or 6-membered aryl ring wherein 1, 2 or 3 of the ring atoms are selected from nitrogen, oxygen and sulfur. Particular examples of 5- or 6-membered heteroaryl ring systems are furan (preferably 2-furyl when AR in 2-(AR)ethenyl), pyrrole, pyrazole, imidazole, triazole, pyrimidine (preferably pyrimidin-2-yl), pyridaziie, pyridine (preferably pyrid-2-yl), isoxazole, oxazole, isothiazole, thiazole and thiophene (preferably 2-thienyl when AR in 2-(AR)ethenyl).
In this specification a xe2x80x985/6 or 6/6 bicyclic heteroaryl ring systemxe2x80x99 and xe2x80x98heteroaryl (bicyclic) ringxe2x80x99 means an aromatic bicyclic ring system comprising a 6-membered ring fused to either a 5 membered ring or another 6 membered ring, the bicyclic ring system containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. Particular examples of 5/6 and 6/6 bicyclic ring systems are indole, benzofuran, benzoimidazole, benzothiophene, benzisothiazole, benzoxazole, benzisoxazole, pyridoimidazole, pyrimidoimidazole, quinoline, quinoxaline, quinazoline, phthalazine, cinnoline and naphthyridine.
In this specification a xe2x80x984-, 5- or 6-membered cycloalkyl ringxe2x80x99 means a cyclobutyl, cyclopentyl or cyclohexyl ring; and a xe2x80x985- or 6-membered cycloalkenyl ringxe2x80x99 a means cyclpentenyl or cyclohexenyl ring.
In this specification the term xe2x80x98alkylxe2x80x99 includes straight chained and branched structures. For example, (1-6C)alkyl includes propyl, isopropyl and tert-butyl. However, references to individual alkyl groups such as xe2x80x9cpropylxe2x80x9d are specific for the straight chained version only, and references to individual branched chain alkyl groups such as xe2x80x9cisopropylxe2x80x9d are specific for the branched chain version only. A similar convention applies to other radicals, for example halo(1-4C)alkyl includes 1-bromoethyl and 2-bromoethyl.
Particular optional substituents for alkyl, phenyl (and phenyl containing moieties) and naphthyl groups and ring carbon atoms in heteroaryl (mono or bicyclic) rings in R11, R12, R1 and AR include halo, (1-4C)alkyl, hydroxy, nitro, carbamoyl, (1-4C)alkylcarbarnoyl, di-((1-4C)alkyl)carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-4C)alkyl S(O)qxe2x80x94, (wherein q is 0, 1 or 2), carboxy, (1-4C)alkoxycarbonyl, (2-4C)alkenyl, (2-4C)alkynyl (1-4C)alkanoyl, (1-4C)alkoxy, (1-4C)alkanoylamino, benzoylamino, benzoyl, phenyl (optionally substituted by up to three substituents selected from halo, (1 -4C)alkoxy or cyano), furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino(1-4C)alkyl, (1-4C)alkoxyimino(1-4C)alkyl, hydroxy-(1-4C)alkyl, halo-(1-4C)alkyl, nitro(1-4C)alkyl, amino(1-4C)alkyl, cyano(1-4C)alkyl, (1-4C)alkanesulfonamido, aminosulfonyl, (1-4C)alkylaminosulfonyl and di-((1-4C)alkyl)aminosulfonyl. The phenyl and naphthyl groups and heteroaryl (mono- or bicyclic) rings in R11, Ri and AR may be mono- or disubstituted on ring carbon atoms with substituents independently selected from the above list of particular optional substituents.
Particular optional substituents for ring nitrogen atoms in heteroaryl groups in R11, R12, Ri and AR and in the nitrogen-containing rings in CY, which can be substituted without becoming quaternised include (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and (1-4C)alkanoyl.
Examples of halo groups include fluoro, chloro and bromo; examples of (1-4C)alkyl, include methyl, ethyl, and propyl and isopropyl; examples of (1-6C)alkyl include methyl, ethyl, propyl, isopropyl, pentyl and hexyl; examples of (1-10C)alkyl include methyl, ethyl, propyl, isopropyl, pentyl, hexyl, heptyl, octyl and nonyl; examples of (1-4C)alkylamino include methylamino, ethylamino and propylamino; examples of di-((1-4C)alkyl)amino include dimethylamino, N-ethyl-N-methylamino, diethylamino, N-methyl-N-propylamino and dipropylamino; examples of (1-4C)alkylS(O)qxe2x80x94 wherein q is 0, 1 or 2 include methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulifonyl and ethylsulfonyl; examples of (1-4C)alkanesulfonyloxy include methylsulfonyloxy, ethylsulfonyloxy and propylsulfonyloxy; examples of (1-4C)alkylthio include methylthio and ethylthio; examples of (1-4C)alkylsulfonyl include methylsulfonyl and ethylsulfonyl; examples of (1-4C)alkylaminocarbonyloxy include methylaminocarbonyloxy and ethylaminocarbonyloxy; examples of (1-4C)alkanoylamino-(1-4C)alkyl include formamidomethyl, acetamidomethyl and acetamidoethyl; examples of (1-6C)alkoxy-(1-6C)alkyl include methoxymethyl, ethoxymethyl and 2-methoxyethyl; examples of (1-4C)alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl; examples of (1-4C)alkanoyloxy include acetyloxy and propionyloxy; examples of (1-4C)alkoxy include methoxy, ethoxy, propoxy and tert-butoxy; examples of (1-6C)alkoxy and (1-10C)alkoxy include methoxy, ethoxy, propoxy, tert-butoxy and pentoxy, examples of hydroxy-(2-6C)alkoxy include 2-hydroxyethoxy and 3-hydroxypropoxy: examples of (1-4C)alkylamino-(2-6C)alkoxy include 2-methylaminoethoxy and 2-ethylaminoethoxy; examples of di-(1-4C)alkylamino-(2-6C)alkoxy include 2-dimethylaminoethoxy and 2-diethylaminoethoxy; examples of (1-4C)alkoxy-(1-4C)alkoxy and (1-6C)alkoxy-(1-6C)alkoxy include methoxymethoxy, 2-methoxyethoxy, 2-ethoxyethoxy and 3-methoxypropoxy; examples of (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy include 2-(methoxymethoxy)ethoxy, 2-(2-methoxyethoxy)ethoxy; 3-(2-methoxyethoxy)propoxy and 2-(2-ethoxyethoxy)ethoxy; examples of (1-4C)alkanoylamino and (1-6C)alkanoylamino include formamido, acetamido and propionylamino: examples of (1-4C)alkoxycarbonylamino include methoxycarbonylamino and ethoxycarbonylamino; examples of N-(1-4C)alkyl-N-(2-6C)alkanoylamino include N-methylacetamido, N-ethylacetamido and N-methylpropionamido; examples of (1-4C)alkylS(O)pNHxe2x80x94 wherein p is 1 or 2 include methylsulfinylamino, methylsulfonylamino, ethylsulfinylamino and ethylsulfonylamino; examples of (1-4C)alkylS(O)p((1-4C)alkyl)NHxe2x80x94 wherein p is 1 or 2 include methylsulfinylmethylamino, methylsulfonylmethylamino, 2-(ethylsulfinyl)ethylamino and 2-(ethylsulfonyl)ethylamino; examples of fluoro(1-4C)alkylS(O)pNHxe2x80x94 wherein p is 1 or 2include trifluoromethylsulfinylamino and trifluoromethylsulfonylamino; examples of fluoro(1-4C)alkylS(O)p((1-4C)alkyl)NHxe2x80x94 wherein p is 1 or 2 include trifluoromethylsulfinylmethylamino and trifluoromethylsulfonylmethylamino examples of (1-4C)alkoxy(hydroxy)phosphoryl include methoxy(hydroxy)phosphoryl and ethoxy(hydroxy)phosphoryl; examples of di-(1-4C)alkoxyphosphoryl include di-methoxyphosphoryl, di-ethoxyphosphoryl and ethoxy(methoxy)phosphoryl; examples of 2-(1-4C)alkylethenyl include 2-methylethenyl and 2-ethylethenyl; examples of 2-((1-4C)alkoxycarbonyl)ethenyl include 2-(methoxycarbonyl)ethenyl and 2-(ethoxycarbonyl)ethenyl; examples of 2-cyano-2-((1-4C)alkyl)ethenyl include 2-cyano-2-methylethenyl and 2-cyano-2-ethylethenyl; examples of 2-((1-4C)alkylaminocarbonyl)ethenyl include 2-(methylaminocarbonyl)ethenyl and 2-(ethylaminocarbonyl)ethenyl; examples of benzyloxy(1-4C)alkyl include benzyloxymethyl and benzyloxyethyl; examples of phenyl(1-4C)alkyl include benzyl and phenethyl; examples of phenylS(O)q wherein q is 0, 1 or 2 are phenylthio, phenylsulfinyl and phenylsulfonyl respectively; examples of(1-4C)alkylcarbamoyl include methylcarbamoyl and ethylcarbamoyl; examples of di((1-4C)alkyl)carbamoyl include di(methyl)carbamoyl and di(ethyl)carbamoyl; examples of a (3-4C)alkylene chain are trimethylene or tetramethylene; examples of (2-4C)alkenyl include allyl and vinyl, examples of (2-4C)alkynyl include ethynyl and 2-propynyl; examples of (1-4C)alkanoyl include formyl, acetyl and propionyl; examples of hydroxyimino(1-4C)alkyl include hydroxyiminomethyl, 2-(hydroxyimino)ethyl and 1-(hydroxyimino)ethyl; examples of (1-4C)alkoxyimino-(1-4C)alkyl include methoxyiminomethyl, ethoxyiminomethyl, 1-(methoxyimino)ethyl and 2-(methoxyimino)ethyl; examples of hydroxy(1-4C)alkyl and hydroxy(1-6C)alkyl include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl and 3-hydroxypropyl; examples of halo(1-4C)alkyl include, halomethyl, 1-haloethyl, 2-haloethyl, and 3-halopropyl; examples of nitro(1-4C)alkyl include nitromethyl, 1-nitroethyl, 2-nitroethyl and 3-nitropropyl; examples of amino(1-4C)alkyl include aminomethyl, 1-aminoethyl, 2-aminoethyl and 3-aminopropyl; examples of cyano(1-4C)alkyl include cyanomethyl, 1-cyanoethyl, 2-cyanoethyl and 3-cyanopropyl; examples of (1-4C)alkanesulfonamido include methanesulfonamido and ethanesulfonamido; examples of (1-4C)alkylaminosulfonyl include methylaminosulfonyl and ethylaminosulfonyl; examples of di-(1-4C)alkylaminosulfonyl include dimethylaminosulfonyl, diethylaminosulfonyl and N-methyl-N-ethylaminosulfonyl; and examples of (4-10C)cycloalkylsulfonyl include cyclopentylsulfonyl and cyclohexylsulfonyl.
Suitable pharmaceutically-acceptable salts include acid addition salts such as methanesulfonate, fumarate, hydrochloride, hydrobromide, citrate, maleate and salts formed with phosphoric and sulfuric acid. In another aspect suitable salts are base salts such as an alkali metal salt for example sodium, an alkaline earth metal salt for example calcium or magnesium, an organic amine salt for example triethylamine, morpholine, N-methylpiperidine, N-ethylpiperidine, procaine, dibenzylamine, N,N-dibenzylethylamine or amino acids for example lysine. There may be more than one cation or anion depending on the number of charged functions and the valency of the cations or anions. A preferred pharmaceutically-acceptable salt is the sodium salt.
However, to facilitate isolation of the salt during preparation, salts which are less soluble in the chosen solvent may be preferred whether pharmaceutically-acceptable or not.
The compounds of the formula (I) may be administered in the form of a pro-drug which is broken down in the human or animal body to give a compound of the formula (I). Examples of pro-drugs include in-vivo hydrolysable esters of a compound of the formula (I).
An in-vivo hydrolysable ester of a compound of the formula (I) containing carboxy or hydroxy group is, for example, a pharmaceutically-acceptable ester which is hydrolysed in the human or animal body to produce the parent acid or alcohol. Suitable pharmaceutically-acceptable esters for carboxy include (1-6C)alkoxymethyl esters for example methoxymethyl. (1-6C)alkanoyloxymethyl esters for example pivaloyloxymethyl, phthalidyl esters, (3-8C)cycloalkoxycarbonyloxy(1-6C)alkyl esters for example 1-cyclohexylcarbonyloxyethyl; 1,3-dioxolen-2-onylmethyl esters for example 5-methyl-1,3-dioxolen-2-onylmethyl; and (1-6C)alkoxycarbonyloxyethyl esters for example 1-methoxycarbonyloxyethyl and may be formed at any carboxy group in the compounds of this invention.
An in-vivo hydrolysable ester of a compound of the formula (I) containing a hydroxy group includes inorganic esters such as phosphate esters and xcex1-acyloxyalkyl ethers and related compounds which as a result of the in-vivo hydrolysis of the ester breakdown to give the parent hydroxy group. Examples of (x-acyloxyalkyl ethers include acetoxymethoxy and 2,2-dimethylpropionyloxymethoxy. A selection of in-vivo hydrolysable ester forming groups for hydroxy include alkanoyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl, alkoxycarbonyl (to give alkyl carbonate esters), dialkylearbamoyl and N-(dialkylaminoethyl)-N-alkylcarbamoyl (to give carbamates), dialkylaminoacetyl and carboxyacetyl. Examples of substituents on benzoyl include morpholino and piperazino linked from a ring nitrogen atom via a methylene group to the 3- or 4- position of the benzoyl ring.
The compounds of the present invention have a chiral centre at the C-5 position of the oxazolidinone ring. The pharmaceutically active enantiomer is of the formula: 
The present invention includes the pure enantiomer depicted above or mixtures of the 5R and 5S enantiomers, for example a racemic mixture. If a mixture of enantiomers is used, a larger amount (depending upon the ratio of the enantiomers) will be required to achieve the same effect as the same weight of the pharmaceutically active enantiomer. For the avoidance of doubt the enantiomer depicted above could be either 5R or 5S depending upon the value of R1. For example, when R1 is acetamido, the enantiomer depicted above is the 5S enantiomer.
Furthermore, some compounds of the formula (I) may have other chiral centres, and some compounds of the formula (I) may exist as one or more regioisomers. It is to be understood that the invention encompasses all such optical, diastereo- and regio-isomers that possess antibacterial activity.
The invention relates to all tautomeric forms of the compounds of the formula (I) that possess antibacterial activity.
It is also to be understood that certain compounds of the formula (I) can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms which possess antibacterial activity.
Particularly preferred compounds of the invention comprise a compound of the formula (I), or a pharmaceutically-acceptable salt thereof, wherein the substituents T,  greater than Axe2x80x94Bxe2x80x94, R1 to R16 and other optional substituents mentioned above have the values disclosed hereinbefore, or any of the following values:
(a) Preferably R1 is of the formula xe2x80x94NHC(xe2x95x90O)Ra wherein Ra is hydrogen, methoxy, chloromethyl, dichloromethyl, cyanomethyl, methoxymethyl, acetyimethyl, methylamino, dimethylamino or (1-4C)alkyl.
(b) Yet more preferably R1 is of the formula xe2x80x94NHC(xe2x95x90O)(1-4C)alkyl.
(c) Most preferably R1 is acetamido.
(d) Preferably, R2 and R3 are hydrogen.
(e) More preferably one of R2 and R3 is hydrogen and the other is fluoro.
(f) In another aspect both R2 and R3 are fluoro.
(g) Preferably T is of the formula (IB) or (IC).
(h) More preferably T is of the formula (IB) wherein m is 0.
(i) Preferably R6 is (1-4C)alkyl, hydroxy-(1-4C)alkyl, AR-oxymethyl and Ar-thiomethyl.
Especially preferred is AR when it is optionally substituted phenyl, phenyl(1-4C)alkyl, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole or thiophene.
(j) When T is of the formula (IA), (IB) or (IC) and R5 and R6 are linked to give a group of the formula (IE) to (IT) so that a 5- or 6-membered ring is formed which is fused to the ring shown in (IA), (IB) or (IC) to give a bicyclic ring structure, T is preferably of the formula (IA) and (IB) wherein m is 0,  greater than Axe2x80x94Bxe2x80x94 is preferably of the formula  greater than CHxe2x80x94CH2 or  greater than C(R4)CH2xe2x80x94 (wherein R4 is preferably methyl) (when T is of the formula (IA)) and  greater than Cxe2x95x90CHxe2x80x94 (when T is of the formula (IB)), and R5 and R6 are preferably linked to give a group of the formula (IE) to (IK). Thus, when R5 and R6 are linked, 5/4- and 5/5- membered bicyclic rings are preferably formed.
(k) When T is of the formula (IA), (IB) or (IC) and R5 and R6 are linked to give a group of the formula (IL) to (IT) so that a 6-membered ring is formed which is fused to the ring shown in (IA), (IB) or (IC) to give a bicyclic ring structure, T is preferably of the formula (IA) and (IB) wherein m is 0,  greater than Axe2x80x94Bxe2x80x94 is preferably of the formula  greater than CHxe2x80x94CH2 or  greater than C(R4)CH2xe2x80x94 (wherein R4 is preferably methyl) (when T is of the formula (IA)) and  greater than Cxe2x95x90CHxe2x80x94 (when T is of the formula (IB)), and R5 and R6 are preferably linked to give a group of the formula (IR) or (IS).
(l) When T is of the formula (IA), (IB) or (IC) and R5 and R6 are linked to give a group of the formula (IE) to (IT, D is preferably  greater than C(R7)(R8) (wherein R7 and R8 are preferably hydrogen), xe2x80x94Oxe2x80x94 or xe2x80x94NR9 (wherein R9 is preferably (1-10C)alkyl or phenyl) and E is preferably  greater than Cxe2x95x90O.
(m) Preferably  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94 when T is of the formula (IB) and (IC).
(n) Preferably  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than C(R4)CH2xe2x80x94 when T is of the formula (IA), and R4 is preferably methyl.
(o) When T is of the formula (IA), (IB) and (IC) R5 is preferably hydrogen, cyano, AR, R10COxe2x80x94 or R10SO2xe2x80x94 wherein R10 is preferably hydrogen or (1-10C)alkyl (optionally substituted by hydroxy, (1-10C)alkoxy, (1-4C)alkanoyl and (1-4C)alkoxycarbonyl).
(p) When T is of the formula (IA), (IB) and (IC) R5 is preferably hydrogen, cyano, benzyl, pyrimidyl, imidazolyl, triazolyl, methoxycarbonyl, tert-butoxycarbonyl, hydoxyacetyl, acetyloxymethylcarbonyl, methoxyacetyl, methoxalyl, or methanesulfonyl.
(q) Preferred substituents for phenyl and carbon atoms in heteroaryl (mono- and bicyclic) ring systems include halo, (1-4C)alkyl, hydroxy, nitro, amino, cyano, (1-4C)alkylS(O)pxe2x80x94 and (1-4C)alkoxy.
(r) Preferred optional substituents for (1-10C)alkyl in R11 are hydroxy, cyano, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-4C)alkylS(O)p (wherein p is 1 or 2), carboxy, (1-4C)alkoxycarbonyl, (1-4C)alkoxy, piperazino or morpholino.
(s) Preferred optional substituents for (1-6C)alkyl in R12 are hydroxy, (1-4C)alkoxy, cyano, amino, (1-4C)alkylamino, di(1-2C)alkylamino, (1-4C)alkylS(O)pxe2x80x94 (wherein p is 1 or 2),
(t) Preferably the ring systems in AR are unsubstituted.
(u) Preferably the 5/6 and 6/6 bicyclic ring systems in AR are unsubstituted.
(v) Preferably the 5- or 6-membered heteroaryl rings in AR, R1 and R11 are unsubstituted.
(w) Preferably the 5- or 6-membered heteroaryl in R11 is pyridyl or imidazol-1-yl.
(x) Preferably R12 is (1-6C)alkyl. Most preferably R12 is tert-butyl or methyl.
(y) Preferably R13 is cyano or fluoro.
(z) Preferably R14 is hydrogen.
(a1) Preferably CY is naphthoxy, especially naphth-1-oxy or naphth-2-oxy.
(b1) Especially preferred is AR when it is optionally substituted phenyl, phenyl(1-4C)alkyl, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole or thiophene.
Therefore, an especially preferred compound of the present invention is of the formula (IU) wherein R1 is acetamido, one of R2 and R3 is hydrogen and the other is fluoro, T is of the formula (IB) (wherein m is 0),  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94, R6 is (1-4C)alkyl, hydroxy-(1-4C)alkyl, AR-oxymethyl and Ar-thiomethyl, R5 is hydrogen, cyano, AR, R10COxe2x80x94 or R10SO2xe2x80x94 wherein R10 is preferably hydrogen or (1-10C)alkyl (optionally substituted by hydroxy, (1-10C)alkoxy, (1-4C)alkanoyl and (1-4C)alkoxycarbonyl), or a pharmaceutically-acceptable salt thereof.
A further especially preferred compound of the present invention is of the formula (IU) wherein R1 is acetamido, one of R2 and R3 is hydrogen and the other is fluoro, T is of the formula (IB) (wherein m is 0),  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94, R6 is benzyloxycarbonyl, (1-4C)alkoxycarbonyl, hydroxy-(1-4C)alkyl, AR-oxymethyl (especially benzoyloxymethyl) and Ar-thiomethyl (especially pyrimidin-2-ylthiomethyl), R5 is hydrogen, trityl, cyano, acetoxyacetyl, (1-6C)alkoxycarbonyl, AR (especially pyrimidin-2-yl), R10OCOxe2x80x94 or R10SO2xe2x80x94 wherein R10 is preferably hydrogen or (1-10C)alkyl (optionally substituted by benzyloxy or hydroxy), or a pharmaceutically-acceptable salt thereof.
A further especially preferred compound of the present invention is of the formula (IU) wherein R1 is acetamido, one of R2 and R3 is hydrogen and the other is fluoro, T is of the formula (IA) and (IB) (wherein mn is 0),  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CH2 or  greater than C(R4)CH2xe2x80x94 (wherein R4 is preferably methyl) (when T is of the formula (IA)) and  greater than Cxe2x95x90CHxe2x80x94 (when T is of the formula (IB)), and R5 and R6 are linked to give a group of the formula (IE) to (IK) so that a 5-membered ring is formed which is fused to the ring shown in (IA) or (IB) to give a 5/4- and 5/5-bicyclic ring structure, or a pharmaceutically-acceptable salt thereof.
A further especially preferred compound of the present invention is of the formula (IU) wherein R1 is acetamido, one of R2 and R3 is hydrogen and the other is fluoro, T is of the formula (IB) (wherein m is 0),  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94, and R5 and R6 are linked to give a group of the formula (IE) to (IK) so that a 5-membered ring is formed which is fused to the ring shown in (IB) to give a 5/5- bicyclic ring structure, or a pharmaceutically-acceptable salt thereof. Particularly preferred 5/5- bicyclic ring structures are dihydropyrrolo[1,2c]oxazole and 1,2,3,7a-tetrahydropyrrolo[1,2c]imidazole, especially with an oxo substituent on the carbon atom between the two heteroatoms.
In further aspects there are provided any of the above especially preferred compounds, or a pharmaceutically-acceptable salt thereof, wherein both R2 and R3 are hydrogen, or both are fluoro, or R2 and R3 are independently hydrogen or fluoro.
Particular compounds of the present invention are:
N-((5S)-3-(4-(2S-benzyloxycarbonyl-1-trityl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-benzyloxymethylcarbonyl-2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-acetoxyacetyl-S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-methylsulphonyl-2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S )-3-(4-(1-cyano-2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-formyl-2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-hydroxyacetyl-2S-benzyloxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-(pyrimidin-2-yl)-2S-ethoxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-ethoxycarbonyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-hydroxymethyl-1-trityl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-(pyrimidin-2-yl)thiomethyl-1-trityl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-formyl-2S-(pyrimidin-2-yl)thiomethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-cyano-2S-(pyrimidin-2-yl)thiomethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-acetoxyacetyl-2S-(pyrimidin-2-yl)thiomethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-tert-Butoxycarbonyl-2S- tert-butyldimethylsilyloxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-tert-Butoxycarbonyl-2S-tert-butyldimethylsilyloxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-tert-Butoxycarbonyl-2S-hydroxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-tert-Butoxycarbonyl-2S-tert-butyldiphenylsilyloxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-tert-Butoxycarbonyl-2S-benzoyloxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-benzoyloxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide,
N-((5S)-3-(4-(2S-benzoyloxymethyl-1-cyano-2,5-dihydropyrrol-4-yl )phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide,
N-((5S)-3-(4-(2S-benzoyloxymethy-1-1-formyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(2S-hydroxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-formyl-2S-hydroxymethyl-2,5-dihydropyrrol-4-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-Benzyl-2RS-benzyloxymethyl-azetidin-3-y l)phenyl-2-oxooxazolidin-5-ylmethyl)acetamide; or a pharmaceutically-acceptable salt thereof.
Of the above particular compounds, the compounds of Examples 23, 24, 25, 32, 40 and 41 described hereinafter, or a pharmaceutically-acceptable salt thereof, are especially preferred.
Where a mixture of isomers is described the invention includes the mixture and the particular individual isomers.
For assistance in naming compounds containing a bicyclic ring the following parent ring structures are provided by way of example: 
Further particular compounds of the present invention containing a bicyclic ring are:
N-((5S)-3-(4-(1,4-dioxo-1,3,4,6,9,9a-hexahydro-pyrido[2.1c][1,4]oxazin-8-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1,3-dioxo-2-phenyl-1,2.3,5,8,8a-hexahydroimidazo[1,5a]pyridin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1,3-dioxo-2-ethyl-1,2,3,5,8,8a-hexahydroimidazo[1,5a]pyridin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4a]pyridin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-oxo-1,5,6,7,8,8a-hexahydrooxazolo[3,4a]pyridin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-((7aS)[3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-((7aS)[3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-((7aS)[3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-((7aS)[5H]-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-((7aR)[3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([3H,5H]-3-oxo-pyrrolo[1,2-c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([3H,5H]-3-oxo-pyrrolo[1,2-c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([3H,5H]-3-oxo-pyrrolo[1,2-c]oxazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c3]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-methyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-methyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-methyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-ethyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-ethyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-ethyl-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-methyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-methyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-methyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-ethyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-ethyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-ethyl-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-hydroxy-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-hydroxy-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-hydroxy-3-oxo-1,2,3,7a-tetrahydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-2-hydroxy-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-2-hydroxy-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-2-hydroxy-3-oxo-2,3-dihydropyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([3H,5H]-3-oxo-pyrrolo[1,2-c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([3H,5H]-3-oxo-pyrrolo[1,2c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([3H,5H]-3-oxo-pyrrolo[1,2c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2-c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([3H,5H]-3-oxo-1,7a-dihydropyrrolo[1,2c]thiazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(3-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(3-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(3-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(3-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-hydroxymethyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-methyl-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-bromo-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-bromo-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-bromo-[5H]-pyrrolo[1,2-c]imidazol-6-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1H]-3-oxo-3,4,8,8a-tetrahydropyrrolo[2,1-c]oxazin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-([1H]-3-oxo-3,4,8,8a-tetrahydropyrrolo[2,1-c]oxazin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-([1H]-3-oxo-3,4,8,8a-tetrahydropyrrolo[2,1-c]oxazin-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-fluoro-[3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3,5-difluoro-[3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-hydroxymethyl-[3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-hydroxymethyl-[3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-hydroxymethyl-[3H]-3-oxo-1,5,8,8a-tetrahydrooxazolo-3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-([3H]-3-oxo-5,8-dihydroxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-fluoro-[3H]-3-oxo-5,8-dihydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3,5-difluoro-[3H]-3-oxo-5,8-dihydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-hydroxymethyl-[3H]-3-oxo-5,8-dihydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-hydroxymethyl-[3H]-3-oxo-5,8-dihydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-hydroxymethyl-[3H]-3-oxo-5,8-dihydrooxazolo[3,4-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-bromo-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-bromo-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-bromo-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-bromo-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-bromo-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-bromo-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-hydroxymethyl-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-hydroxymethyl-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-hydroxymethyl-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-hydroxymethyl-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(3-hydroxymethyl-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(3-hydroxymethyl-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(3-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(3-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(3-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(3-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(3-cyano-5,8-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(4-(1-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3-fluoro-4-(1-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide;
N-((5S)-3-(3,5-difluoro-4-(1-cyano-5,6-dihydroimidazo[1,5-a]pyrid-7-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide; or a pharmaceutically-acceptable salts thereof.
Of the above particular compounds, the compounds of Examples 44, 45, 47, 48 and 49 described hereinafter are especially preferred.
Where a mixture of isomers is described, the invention includes the mixture and the particular individual isomers.
In a further aspect the present invention provides a process for preparing a compound of formula (I) or a pharmaceutically-acceptable salt thereof. The compounds of formula (I) may be prepared by deprotecting a compound of formula (II): 
wherein R2 and R3 are as hereinabove defined, R20 is R1 or protected R1 and T1 is T in which functional groups are optionally protected; and thereafter, if necessary, forming a pharmaceutically-acceptable salt or in-vivo-hydrolysable ester.
Protecting groups may be removed by any convenient method as described in the literature or known to the skilled chemist as appropriate for the removal of the protecting group in question, such methods being chosen so as to effect removal of the protecting group with minimum disturbance of groups elsewhere in the molecule.
Specific examples of protecting groups are given below for the sake of convenience and are included as a further feature of the invention. xe2x80x9cLowerxe2x80x9d signifies that the group to which it is applied preferably has 1-4 carbon atoms. It will be understood that these examples are not exhaustive. Where specific examples of methods for the removal of protecting groups are given below these are similarly not exhaustive. The use of protecting groups and methods of deprotection not specifically mentioned is of course within the scope of the invention.
A carboxy protecting group may be the residue of an ester-forming aliphatic or araliphatic alcohol or of an ester-forming silanol (the said alcohol or silanol preferably containing 1-20 carbon atoms).
Examples of carboxy protecting groups include straight or branched chain (1-12C)alkyl groups (eg isopropyl, t-butyl); lower alkoxy lower alkyl groups (eg methoxymethyl, ethoxymethyl, isobutoxymethyl; lower aliphatic acyloxy lower alkyl groups, (eg acetoxymethyl, propionyloxymethyl, butyryloxymethyl, pivaloyloxymethyl); lower alkoxycarbonyloxy lower alkyl groups (eg 1-methoxycarbonyloxyethyl, 1-ethoxycarbonyloxyethyl); aryl lower alkyl groups (eg p-methoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, benzhydryl and phthalidyl); tri(lower alkyl)silyl groups (eg trimethylsilyl and t-butyldimethylsilyl); tri(lower alkyl)silyl lower alkyl groups (eg trimethylsilylethyl); and (2-6C)alkenyl groups (eg allyl and vinylethyl).
Methods particularly appropriate for the removal of carboxyl protecting groups include for example acid-, metal- or enzymically-catalysed hydrolysis.
Examples of hydroxy protecting groups include lower alkenyl groups (eg allyl); lower alkanoyl groups (eg acetyl); lower alkoxycarbonyl groups (eg t-butoxycarbonyl); lower alkenyloxycarbonyl groups (eg allyloxycarbonyl); aryl lower alkoxycarbonyl groups (eg benzoyloxycarbonyl, p-methoxybenzyloxycarbonyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl); tri lower alkyl/arylsilyl groups (eg trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl); aryl lower alkyl groups (eg benzyl) groups; and triaryl lower alkyl groups (eg triphenylmethyl).
Examples of amino protecting groups include formyl, aralkyl groups (eg benzyl and substituted benzyl, eg p-methoxybenzyl, nitrobenzyl and 2,4-dimethoxybenzyl, and triphenylmethyl); di-p-anisylmethyl and furylmethyl groups; lower alkoxycarbonyl (eg t-butoxycarbonyl); lower alkenyloxycarbonyl (eg allyloxycarbonyl); aryl lower alkoxycarbonyl groups (eg benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl; trialkylsilyl (eg trimethylsilyl and t-butyldimethylsilyl); alkylidene (eg methylidene); benzylidene and substituted benzylidene groups.
Methods appropriate for removal of hydroxy and amino protecting groups include, for example, acid-, metal- or enzymically-catalysed hydrolysis, for groups such as o-nitrobenzyloxycarbonyl, photolytically and for groups such as silyl groups, fluoride. Benzyl protecting groups may be removed by use of a BCl3xe2x80x94Me2S complex.
Examples of protecting groups for amide groups include aralkoxymethyl (eg. benzyloxymethyl and substituted benzyloxymethyl); alkoxymethyl (eg. methoxymethyl and trimethylsilylethoxymethyl); tri alkyl/arylsilyl (eg. trimethylsilyl, t-butyldimethylsily, t-butyldiphenylsilyl); tri alkyl/arylsilyloxymethyl (eg. t-butyldimethylsilyloxymethyl, t-butyldiphenylsilyloxymethyl); 4-alkoxyphenyl (eg. 4-methoxyphenyl); 2,4-di(alkoxy)phenyl (eg. 2,4-dimethoxyphenyl); 4-alkoxybenzyl (eg. 4-methoxybenzyl); 2,4-di(alkoxy)benzyl (eg. 2,4-di(methoxy)benzyl); and alk-1-enyl (eg. allyl, but-1-enyl and substituted vinyl eg. 2-phenylvinyl).
Aralkoxymethyl, groups may be introduced onto the amide group by reacting the latter group with the appropriate aralkoxymethyl chloride, and removed by catalytic hydrogenation. Alkoxymethyl, tri alkyl/arylsilyl and tri alkyl/silyl groups may be introduced by reacting the amide with the appropriate chloride and removing with acid, or in the case of the silyl containing groups fluoride ions. The alkoxyphenyl and alkoxybenzyl groups are conveniently introduced by arylation or alkylation with an appropriate halide and removed by oxidation with ceric ammonium nitrate. Finally alk-1-enyl groups may be introduced by reacting the amide with the appropriate aldehyde and removed with acid.
For further examples of protecting groups see one of the many general texts on the subject, for example, xe2x80x98Protective Groups in Organic Synthesisxe2x80x99 by Theodora Green (publisher: John Wiley and Sons).
In another aspect of the present invention the compounds of the formulae (I) and (II); pharmaceutically acceptable salts thereof and in-vivo-hydrolysable esters thereof can be prepared by the following processes (a) to (o). Certain novel intermediates, for example compounds of the formula (I) or (II) wherein R1 or R10 is hydroxy and amino, and processes for their preparation, are provided as a further feature of the invention.
(a) by modifying a substituent in or introducing a substituent into another compound of formula (I) or (II);
(b) when R1 or R20 is of the formula xe2x80x94NHS(O)n(1-4C)alkyl, wherein n is 1 or 2, by oxidising a compound of the formula (I) or (II) wherein n is 0 or, when n is 2 by oxidising a compound of the formula (I) or (II) wherein n is 1;
(c) when R1 or R20 is of the formula xe2x80x94NHC(xe2x95x90O)Rb or xe2x80x94NHS(O)n(1-4C)alkyl, introducing the group xe2x80x94C(xe2x95x90O)Rb or xe2x80x94S(O)n(1-4C)alkyl into a compound of the formula (III): 
xe2x80x83wherein a compound of the formula (III) (i.e. a compound of the formula (I) or (II) wherein R1 or R20 is amino) may be obtained by reducing a compound of the formula (I) or (II) wherein R1 or R20 is azido;
(d) when R1 or R20 is chloro, fluoro, (1-4C)alkanesulfonyloxy, or (1-4C)alkylaminocarbonyloxy, or R20 is of the formula xe2x80x94N(CO2R26)CO(1-4C)alkyl, wherein R26 is (1-4C)alkyl or benzyl; from a compound of the formula (I) and (II) wherein R1 or R20 is hydroxy; wherein a compound of the formula (I) and (II) wherein R1 or R20 is hydroxy may be obtained by reacting a compound of the formula (V) with a compound of formula (VI): 
xe2x80x83wherein R21 is (1-6C)alkyl or benzyl; R22 is of the formula (1-4C)alkyl or xe2x80x94S(O)n(1-4C)alkyl;
(e) when T or T1 is of the formula (IB) and (IC) and contains  greater than Axe2x80x94Bxe2x80x94 of the formula  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94, by reacting (using Pd coupling chemistry) a compound of the formula (VII) with a compound of the formula (VIIA)or (VIIB) wherein  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94: 
xe2x80x83wherein L1 is an iodo or triflate leaving group (when Y is a trialkyltin residue or a boronate acid or ester residue) and L1 is a trialkyltin residue or a boronate acid or ester residue (when Y is an iodo or triflate leaving group); Y is an iodo or triflate leaving group (when L1 is a trialkyltin residue or a boronate acid or ester residue) and Y is a trialkyltin residue or a boronate acid or ester residue (when L1 is an iodo or triflate leaving group);
(f) when T or T1 contains  greater than Axe2x80x94Bxe2x80x94 of the formula  greater than CHxe2x80x94CH2xe2x80x94 or  greater than CHxe2x80x94CH(R4a)xe2x80x94, by catalytic hydrogenation of a compound of the formula (I) or (II) wherein  greater than Axe2x80x94Bxe2x80x94 is  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94;
(g) when T or T1 contains  greater than Axe2x80x94Bxe2x80x94 of the formula  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a), by elimination of the elements of water, or HOCOR23, or HOSO2R24 from a compound in which  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than C(OH)xe2x80x94CH2xe2x80x94,  greater than C(OCOR23)xe2x80x94CH2xe2x80x94,  greater than C(OSO2R24)xe2x80x94CH2xe2x80x94,  greater than C(OH)xe2x80x94CH(R4a)xe2x80x94,  greater than C(OCOR23)xe2x80x94CH(R4a)xe2x80x94 or  greater than C(OSO2R24)xe2x80x94CH(R4a)xe2x80x94; wherein R23 is (1-4C)alkyl and R24 is an optionally substituted phenyl group;
(h) when T or T1 is of the formula (IA) or (IB) and contains  greater than NR5 where R5 is R10COxe2x80x94, R10SO2xe2x80x94 or R10CSxe2x80x94 and R5 is not linked to R6, by reaction, of a compound of formula (II) in which T or T1 is of the formula (IA) or (IB) and contains  greater than NR5 wherein R5 is hydrogen, with a compound of the formula R10COL2, R10SO2L2 or R10CSL2; wherein L2 is a leaving group (such as, for example, hydroxy or chloro); and when R5 is R10COxe2x80x94 and R10 is amino, (1-4C)alkylamino or di-(1-4C)alkylamino, by reaction with an appropriate isocyanate in an inert solvent (at, or near, ambient temperature);
(i) when R1 or R20 is azido, by reacting a compound of the formula (VIII), wherein R25 is mesyloxy or tosyloxy, with a source of azide; 
(j) when R1 or R20 is chioro, (1-4C)alkylthio or (1-4C)alkoxy, from a compound of the formula (VIII);
(k) when T or T1 is of the formula (IA) wherein R5 is benzyl and  greater than Axe2x80x94Bxe2x80x94 is  greater than CHxe2x80x94CH2xe2x80x94, by reaction of a compound of the formula (IX) 
xe2x80x83with a nitrone of the formula benzyl-N(O)xe2x95x90CHxe2x80x94R6 in the presence of a Cu(I) salt, to give a compound of the formula (X) 
xe2x80x83and subsequent reduction of the compound of the formula (X), (and when G in formula (IX) is nitro or amino, by subsequent formation of the desired oxazolidinone ring using a process such as process (c)); wherein G is (optionally protected) of the formula (XI), nitro or amino; 
(l) when T or T1 is of the formula (IA) wherein R5 is benzyl, and  greater than Axe2x80x94Bxe2x80x94 is  greater than C(R4)xe2x80x94CH2xe2x80x94 (wherein R4 is (1-4C)alkyl) by reaction of a compound of the formula (X) with a compound of the formula R4xe2x80x94L1 (wherein L1 is a leaving group such as chloro, bronco or iodo) in the presence of a base (such as LDA, BuLi or NaH) and subsequent reduction of the compound of the formula (X) (and when G in formula (IX) is nitro or amino, by subsequent formation of the desired oxazolidinone ring using a process such as process (d));
(m) when T or T1 is of the formula (IA) wherein R5 is benzyl, and  greater than Axe2x80x94Bxe2x80x94 is  greater than C(R4)xe2x80x94CH2xe2x80x94 (wherein R4 is hydroxy) by oxidation of a compound of the formula (X) (i.e. with R4 as hydrogen) using a suitable oxidizing agent, such Davis reagent, e.g. an oxaziridine (for example (1S)(+)(10-camphorsulfonyl)oxaziridine) in the presence of a suitable base such as potassium bis(trimethylsilyl)amide (and when G in formula (IX) is nitro or amino, by subsequent formation of the desired oxazolidinone ring using a process such as process (c));
(n) when T or T1 is of the formula (IA) wherein R5 is benzyl, and  greater than Axe2x80x94Bxe2x80x94 is  greater than C(R4)xe2x80x94CH2xe2x80x94 (wherein R4 is halo), from the corresponding compound in which R4 is hydroxy (and when G in formula (IX) is nitro or amino, by subsequent formation of the desired oxazolidinone ring using a process such as process (c));
(o) when T or T1 is of the formula (IB) or (IC) containing  greater than Axe2x80x94Bxe2x80x94 of the formula  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94, and R5 and R6 are linked to give a group of the formula (IE) to (IT), by a process as described in process (e), in which the R5 and R6 groups are linked either before, or after, the coupling reaction between compounds of the formula (VII) and (VIIA) or (VIIB). The skilled chemist will be aware if it is desirable to perform the linking of the R5 and R6 groups before, or after, the coupling reaction between compounds of the formula (VII) and (VIIA) or (VIIB). The skilled chemist will be further aware when suitable protecting groups are desirable to protect specific functionalities in the compounds of the formula (VII) and (VIIA) or (VIIB) during the coupling reaction. Thus, if the R5 and R6 groups are linked before the coupling reaction, suitable protecting groups may, for example, be desirable to protect the R7, R8 and R9 groups during the coupling reaction. Similarly, if the R5 and R6 groups are linked after the coupling reaction, suitable protecting groups (such as tert-butoxycarbonyl (BOC), trimethylsilyl (TMS) or trityl) may be desirable to protect the R5 and R6 groups during the coupling reaction.
Compounds in which T or T1 is of the formula (IB) or (IC) containing  greater than Axe2x80x94Bxe2x80x94 of the formula  greater than CHxe2x80x94CH2xe2x80x94 or  greater than CHxe2x80x94CH(R4a)xe2x80x94, and in which R5 and R6 are linked to give a group of the formula (IE) to (IT), may be obtained by catalytic hydrogenation of the corresponding compound wherein  greater than Axe2x80x94Bxe2x80x94 is  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94.
Compounds in which T or T1 is of the formula (IA), and in which R5 and R6 are linked to give a group of the formula (IE) to (IT) may be obtained by formation of the 4-membered ring according to process (k), removal of the R5 benzyl group, functionalisation of the nitrogen with a suitable R5 group and cyclisation by linking the R5 and R6 groups to form a group of the formula (IE) to (IT).
wherein R1, R2, R3, R4a, R5, R6, R20, Rb and m are as hereinabove defined; n is 0, 1 or 2 unless otherwise stated above; and thereafter if necessary:
i) removing any protecting groups;
ii) forming a pharmaceutically-acceptable salt;
iii) forming an in-vivo hydrolysable ester.
Further details concerning the above processes are given below:
(a) Methods for converting substituents into other substituents are known in the art. For example an alkylthio group may be oxidised to an alkylsulfinyl or alkysulfonyl group, a cyano group reduced to an amino group, a nitro group reduced to an amino group, a hydroxy group alkylated to a methoxy group, a hydroxy group converted to a phenylsulfonyloxy group, a hydroxy group thiomethylated to an arylthiomethyl or a heteroarylthiomethyl group (see, for example, Tet.Lett., 585, 1972), a carbonyl group converted to a thiocarbonyl group (eg. using Lawesson""s reagent), a bromo group converted to an alkylthio group. When R5 is benzyl, the benzyl group may be removed (using 2-chloroethyl chloroformate under von Braun conditions if the compound contains a double bond in  greater than Axe2x80x94Bxe2x80x94 which is to be retained) and the  greater than NH group functionalised to give other values for R5. When R4 is hydroxy, the hydroxy group may be converted to an alkanoyloxy group using Schotten-Baumann conditions. When R4 is (1-4C)alkyl, the (1-4C)alkyl group may be introduced by alkylation of the saturated parent compound. When R4 is halo, the halo group may be introduced by substitution starting from a compound with R4 as hydroxy. In bicyclic ring systems, a double bond in allylic orientation may be prepared by dehydrobromination using a hindered non-nucleophilic base in an inert solvent at a temperature in the range ambient to 100xc2x0 C. It is also possible to convert one R5 group into another R5 group as a final step in the preparation of a compound of the formula (I) or (II) (see the specific Examples).
(b) Compounds of the formula (I) or (II) wherein R1 or R20 is xe2x80x94NHS(O)n(1-4C)alkyl can be prepared by oxidising a compound of the formula (I) or (II) with standard reagents known in the art for the oxidation of a thio group to a sulfinyl or sulfonyl group. For example, a thio group may be oxidised to a sulfinyl group with a peracid such as m-chloroperoxybenzoic acid and oxidising agents such as potassium permanganate can be used to convert a thio group to a sulfonyl group. Compounds of the formula (I) or (II) wherein R1 or R20 is xe2x80x94NHS(1-4C)alkyl can be prepared by reacting compounds of the formula (III) with a reagent such as (1-4C)alkylSCl.
c) When Rb is (1-4C)alkyl, the group xe2x80x94C(xe2x95x90O)(1-4C)alkyl may be introduced into a compound of the formula (III) by standard acetylation procedures. For example, the amino group may be acetylated to give an acetamido group using the Schotten-Baumann procedure i.e. reacting the compound of the formula (I) or (II) wherein R1 or R20 is amino with acetic anhydride in aqueous sodium hydroxide and THF in a temperature range of 0xc2x0 C. to ambient temperature. Preferably the acylation is carried out in situ following the catalytic hydrogenation of a compound of the formula (I) or (II) wherein R1 or R20 is azido, by performing the hydrogenation in the presence of acetic anhydride.
When Rb is hydrogen, the xe2x80x94CHO group may be introduced into the compound of the formula (III) by reacting the latter compound with formic acetic anhydride, in an inert organic solvent such as THF, in a temperature range of 0xc2x0 C. to ambient temperature, or by reacting it with ethyl formate in an inert organic solvent in the temperature range of 50-100xc2x0 C.
When Rb is (1-4C)alkoxy, the xe2x80x94COO(1-4C)alkyl group may be introduced into the compound of the formula (III) by reacting the latter compound with (1-4C)alkyl chloroformate, in the presence of an organic base such as triethylamine, in an organic solvent such as dichloromethane and in a temperature range of 0xc2x0 C. to ambient temperature.
When Rb is amino, the xe2x80x94CONH2 group may be introduced into the compound of the formula (III) by reacting the latter compound either with potassium cyanate in aqueous acid (eg. hydrochloric acid) in a temperature range of ambient temperature to 40xc2x0 C. or with phenyl carbamate in glyme at reflux.
When Rb is chloromethyl, dichloromethyl, cyanomethyl or methoxymethyl, the xe2x80x94C(xe2x95x90O)Rb group may be introduced into the compound of the formula (III) by reacting the latter compound with the appropriate acid chloride under standard conditions. The acid chloride may be prepared from the appropriate acid. When Rb is acetylmethyl, the xe2x80x94C(xe2x95x90O)Rb group may be introduced into the amino compound by reacting the latter compound with diketene, in an inert organic solvent such as THF, in a temperature range of 0xc2x0 C. to ambient temperature.
Alternatively, the compound of the formula (III) may be reacted with the appropriate acid anhydride, in dichloromethane or THF, in the presence of an organic base such as triethylamine and in a temperature range of 0xc2x0 C. to ambient temperature, or the amino compound may be reacted with the appropriate acid in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and an organic base such as triethylamine, in an organic solvent such as dichloromethane, in a temperature range of 0xc2x0 C. to ambient temperature.
When Rb is methylamino, the xe2x80x94CONHMe group may be introduced into the compound of the formula (III) by reacting the latter compound with methyl isocyanate in an organic solvent such as THF or acetonitrile, in a temperature range of 0xc2x0 C. to ambient temperature.
When Rb is dimethylamino, the xe2x80x94CONMe2 group may be introduced into the compound by of the formula (III) by reacting the latter compound with dimethylcarbamoyl chloride and triethylamine in an organic solvent such as THF or acetonitrile, in a temperature range of 0xc2x0 C. to ambient temperature.
Standard reaction conditions for the conversion of a compound of the formula (III) to a compound of the formula (I) or (II) wherein R1 or R20 is sulfonamido are known in the art. For example, a compound of the formula (III) could be converted to a compound of the formula (I) or (II) wherein R1 or R20 is (1-4C)alkyl SO2NHxe2x80x94 by reacting the former compound with a sulfonyl chloride, for example, mesyl chloride, in a mild base such as pyridine or triethylamine.
Alternatively compounds of the formula (I) or (II) wherein R1 or R20 is (1-4C)alkyl SO2NHxe2x80x94 or (1-4C)alkylSONHxe2x80x94 may be prepared by reacting a compound of the formula (III) with a compound of the formula (IV): 
The compound of the formula (IV) may be prepared by oxidising a compound of the formula (IVA): 
with standard oxidising agents known for the conversion of a thio group to a sulfinyl or sulfonyl group.
Compounds of the formula (IVA) can be prepared by reacting phthalimide with an alkylthiochloride ((1-4C)alkylSCl).
A compound of the formula (III) (i.e. a compound of the formula (I) or (II) wherein R1 or R20 is amino) may be obtained by reducing a compound of the formula (I) or (II) wherein R1 or R20 is azido (see later under process (i) for preparation of such compounds). Suitable reducing agents for reducing azido to amino in a compound of the formula (I) or (II) include triethylamine/hydrogen sulfide, triphenylphosphine or phosphite ester, or hydrogen in the presence of a catalyst. More specifically the reduction of the azido group may be carried out by heating it in an aprotic solvent, such as 1,2-dimethoxyethane, in the presence of P(OMe)3 and subsequently heating in 6N aqueous hydrochloric acid, or reacting it with hydrogen in the presence of palladium on carbon in a solvent such as DMF or ethyl acetate. For further details on the reduction of azides to amines see U.S. Pat. No. 4,705,799. The azido compound may be reduced and converted to a compound of the formula (I) or (II), wherein R1 or R10 is acetamido, in situ using acetic anhydride in DMF.
(d) A compound of the formula (I) or (II) wherein R1 or R20 is fluoro may be prepared by reacting a compound of the formula (I) or (II) wherein R1 or R20 is hydroxy (hydroxy compound) with a fluorinating agent such as diethylaminosulfur trifluoride in an organic solvent such as dichloromethane in the temperature range of 0xc2x0 C. to ambient temperature.
When R1 or R20 is chloro, the compound of the formula (I) or (II) may be formed by reacting the hydroxy compound with a chlorinating agent. For example, by reacting the hydroxy compound with thionyl chloride, in a temperature range of ambient temperature to reflux, optionally in a chlorinated solvent such as dichloromethane or by reacting the hydroxy compound with carbon tetrachloride/triphenyl phosphine in dichloromethane, in a temperature range of 0xc2x0 C. to ambient temperature.
The (1-4C)alkanesulfonyloxy compound may be prepared by reacting the hydroxy compound with (1-4C)alkanesulfonyl chloride in the presence of a mild base such as triethylamine or pyridine.
The (1-4C)alkylaminocarbonyloxy compound may be prepared by reacting the hydroxy compound with (1-4C)alkyl cyanate in an organic solvent such as THF or acetonitrile, in the presence of triethylamine, in a temperature range of 0xc2x0 C. to 50xc2x0 C.
A compound of the formula (II) wherein R20 is of the formula xe2x80x94N(CO2R26)CO(1-4C)alkyl is conveniently prepared by reacting a compound of the formula (I) and (II) wherein R1 or R20 is hydroxy with an amide of the formula HN(CO2R26)CO(1-4C)alkyl under Mitsunobu conditions. For example, in the presence of tri-n-butylphosphine and 1,1xe2x80x2-(azodicarbonyl)dipiperidine in an organic solvent such as THF, and in the temperature range 0xc2x0 C.-60xc2x0 C., but preferably at ambient temperature. Details of analogous Mitsunobu reactions are contained in Tsunoda et al, Tet. Letts., 34, 1639, (1993). Amides of the formula HN(CO2R26)CO(1-4C)alkyl may be prepared by standard procedures of organic chemistry which are within the ordinary skill of an organic chemist.
Compounds of the formulae (V) and (VI) are conveniently reacted together (to give the hydroxy compound) in the presence of a strong base such as butyl lithium, lithium hexamethyldisilazide, sodium hydride, or lithium diisopropylamide. The reaction is conveniently carried out in an inert solvent such as tetrahydrofuran (THF), dimethylformamide (DMF), N,N1-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone in a temperature range of xe2x88x9278xc2x0 C. to xe2x88x9250xc2x0 C. for the deprotonation and cyclisation. Suitable values for R21 include ethyl, butyl and benzyl and suitable values for R22 include ethyl and n-propyl, preferably n-propyl.
A compound of the formula (V) is conveniently prepared by reacting a chloroformate of the formula (ClCOOR21) with a compound of the formula (VA): 
The reaction is conveniently carried out in the presence of an inorganic or organic base such as sodium bicarbonate or an amine base such as dimethylaniline, the former in a solvent such as acetone/water and the latter in an organic solvent such as THF, toluene, DMF or acetonitrile.
A compound of the formula (VA), may be prepared by reacting a compound of the formula (VIIA) or (VIIB) with a compound of the formula (VB). 
The reaction between compounds of the formulae (VIIA) or (VIIB) and (VB) wherein L1 is bromo or iodo may be is carried out by treating (VB) with an organolithium species such as 1-butyl methyl in an inert solvent such as THF at a low temperature, such as xe2x88x9278xc2x0 C., followed by the addition of an anhydrous zinc halide such as zinc chloride, in a temperature range of 0xc2x0 C. to ambient temperature, to generate the organozinc chloride (VB), wherein L3 is ZnCl. Treatment of the organozinc chloride in situ with a compound of the formula (VIIA) or (VIIB) followed by a suitable palladium [0] catalyst such as Pd (PPh3)4, in the temperature range of 0xc2x0 C. to ambient temperature, results in the cross-coupled product (VA) after brief treatment with dilute acid to hydrolyse the xe2x80x98stabasexe2x80x99 protected amine.
A compound of the formula (VB) may be prepared by treatment of p-iodo or p-bromoaniline with the xe2x80x98stabasexe2x80x99 reagent (1,2-bis(chlorodimethylsilyl)ethane) in the presence of an organic base such as triethylamine.
(e) The following details concerning process (e) describe the reaction when Y in compound (VII) is a trialkyltin residue or a boronate acid or ester residue and L1 in compounds (VIIA) and (VIIB) is an iodo or triflate leaving group. Process (e) also describes the converse reaction in which Y in compound (VII) is an iodo or triflate leaving group and L1 in compounds (VIIA) and (VIIB) is a trialkyltin residue or a boronate acid or ester residue. Similar details concerning reaction conditions and preparation of starting materials apply (unless otherwise stated) in this converse reaction as apply to the following details.
The reaction between compounds of the formulae (VII) and (VIIA) or (VIIB), wherein Y is trialkyltin and L1 is iodo or triflate is conveniently carried out in the presence of a palladium (0) catalyst such as Pd(PPh3)4 or Pd(dba)3 in a temperature range of 0-115xc2x0 C. Preferably the trialkyltin group is trimethyltin.
When Y is a boronate acid or ester, the reaction may be carried out under conditions known for the Suzuki reaction, i.e. in the presence of a palladium (0) catalyst such as Pd(PPh)3)4 or Pd(dba)3, in a water-miscible organic solvent such as dimethylformamide or 1,2-dimethoxyethane and in the presence of a mild base such as sodium acetate or sodium bicarbonate which is added in water. The reaction is then heated to 80xc2x0 C. Alternatively, silver oxide may be used in place of the base, in which case the reaction may be carried out at a lower temperature. When Y is a boronate ester, preferably L1 is iodo. Suitable boronate esters include lower alkyl and cyclic boronate esters, and may be prepared according to techniques known in the art.
A compound of the formula (VII) wherein Y is trimethylstannyl may be prepared by methods known in the art (for example by using methods similar to those described in patent application Ser. No. WO 9413649 from a compound of the formula (VII) wherein Y is iodo or bromo). Alternatively compounds of the formula (VII) wherein Y is a cyclic boronate ester as in (VIIC): 
may be prepared from a compound of the formula (VII) wherein Y is iodo or bromo, by sequential treatment with a suitable Pd catalyst such as PdCl2(dppf), potassium acetate and the pinacol ester of diboron in a polar solvent such as DMSO (for example see J.Org.Chem., 1995, 60, 7508-7510). When L1 in compounds (VIIA) and (VIIB) is a boronate ester residue, a non-cyclic (lower alkyl) boronate ester is preferred.
A compound of the formula (VII), wherein Y is iodo may be prepared by reacting a compound of the formula (VIID) with iodine monochloride in the presence of trifluoroacetic acid or with iodine and silver triflate: 
When Y is bromo, a compound of the formula (VII) may be prepared by brominating a compound of the formula (VIID) using standard bromination methods. For example, by reacting a compound of the formula (VIID) with N-bromosuccinimide or bromine.
A compound of the formula (VIID) may be prepared by forming the oxazolidinone ring from the amino group of a compound of the formula (VIIE) using a similar method to that described for the preparation of a compound of the formula (I) or (II) from a compound of the formula (VA)xe2x80x94see process (d): 
The resulting compound of the formula (VIID) in which R20 is hydroxy may be converted to other compounds of the formula (VIID) using similar methods to those described for the formation of a compound of the formula (I) or (II) from a compound of the formula (I) or (II) wherein R1 or R20 is hydroxy, via a compound of the formula (III)xe2x80x94see process (c).
A compound of the formula (VIIA) or (VIIB) wherein R5 is protected R5 and L1 is triflate may be prepared by treating a compound of the formula (VIIF) or (VIIG) with lithium diisopropylamide in an inert solvent such as THF, at a low temperature, for example xe2x88x9278xc2x0 C., followed by N-phenyl triflamide (for example, see methods described in Synthesis, 993-95 (1991)). A compound of the formula (VII) in which Y is triflate may not be prepared using this approach. 
wherein R5 is protected R5 and xe2x80x94Axe2x80x94Bxe2x80x94 in (VIIF) and (VIIG) is xe2x80x94Cxe2x80x94CH2xe2x80x94 or xe2x80x94Cxe2x80x94CH(R4a)xe2x80x94.
Alternatively, a compound of the formula (VIIA) or (VIIB) wherein L1 is iodo may be prepared by treating a hydrazone of a compound of formula (VIIF) or (VIIG) with iodine in the presence of triethylamine (for example see methods detailed in Tet. Letts. 24, 1605-1608 (1983)). A compound of the formula (VII) in which Y is iodo may not be prepared using this approach.
Compounds of the formula (VIIA) or (VIIB) wherein R5 is R14CH(R13)(CH2)mxe2x80x94 or AR can be prepared by formation of the ring from the appropriate amine, arylamine or heteroarylamine, by reaction with ethyl acrylate to give the corresponding diethylarylimino-beta-beta-dipropionate, which can then be cyclised under Dickmann conditions to the give corresponding beta-ketoester, followed by decarboxylation with heating in acid (see methods described in J.Chem.Soc. 5110-5118 (1962)).
Alternatively, a compound of the formula (VIIA) or (VIIB) wherein R5 is R14CH(R13)(CH2)mxe2x80x94 or AR may be prepared by reacting an appropriately substituted R14CH(R13)(CH2)mxe2x80x94 or AR compound containing a leaving group such as chloro, bromo or iodo with the appropriate compound of the formula (VIIA), (VIIB), (VIIF) or (VIIG) at an elevated temperature, in an inert solvent and optionally with an acid trapping agent.
(f) Suitable catalysts for the catalytic hydrogenation of a compound of the formula (I) or (II) wherein  greater than Axe2x80x94Bxe2x80x94 is  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94 include Raney nickel, platinum metal or its oxide, rhodium, zinc oxide, palladium-on-charcoal and Wilkinson""s catalyst (RhCl(Ph3P)3. Catalyic hydrogenation is conveniently carried out in the temperature range 0xc2x0 C. to 150xc2x0 C., but preferably at ambient temperature and pressure, unless Wilkinson""s catalytic is used in which case a temperature of approximately 50xc2x0 C. and pressure of approximately 50 atmospheres are preferable.
(g) A compound in which  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than C(OH)xe2x80x94CH2xe2x80x94,  greater than C(OCOR23)xe2x80x94CH2xe2x80x94,  greater than C(OSO2R24)xe2x80x94CH2xe2x80x94,  greater than C(OH)xe2x80x94CH(R4a)xe2x80x94,  greater than C(OCOR23)xe2x80x94CH(R4a)xe2x80x94 or  greater than C(OSO2R24)xe2x80x94CH(R4a)xe2x80x94 may be prepared by reacting an intermediate of the formula (VB) with magnesium to form a Grignard reagent, or alternatively with n-butyl lithium to form a lithiated species, and then reacting the Grignard reagent or lithiated species with a compound of formula (VIIF) or (VIIG). The product (VA), wherein  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than C(OH)CH2xe2x80x94 or  greater than C(OH)CH(R4a)xe2x80x94 may then be elaborated as previously detailed for the compound of the formula (V), but with optional protection of the hydroxyl group.
The dehydration of a compound in which  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than C(OH)xe2x80x94CH2xe2x80x94,  greater than C(OCOR23)xe2x80x94CH2xe2x80x94,  greater than C(OSO2R24)xe2x80x94CH2xe2x80x94,  greater than C(OH)xe2x80x94CH(R4a)xe2x80x94,  greater than C(OCOR23)xe2x80x94CH(R4a)xe2x80x94  greater than C(OSO2R24)xe2x80x94CH(R4a)xe2x80x94 to give a compound of formula (I) or (II) wherein  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than Cxe2x95x90CHxe2x80x94 or  greater than Cxe2x95x90C(R4a)xe2x80x94 may be carried out using agents such as polyphosphoric acid, trifluoroacetic acid, trifluoroacetic anhydride, p-toluenesulfonic acid, sulfuric acid, thionyl chloride etc., in an inert solvent such as toluene, and at elevated temperatures. Suitable protection of the group R20 may be necessary as appropriate.
A compound of the formula (I) or (II) wherein  greater than Axe2x80x94Bxe2x80x94 is of the formula  greater than CHCH(R4a)xe2x80x94 may be prepared from a compound of the formula (I) or (II) wherein  greater than Axe2x80x94Bxe2x80x94 is  greater than Cxe2x95x90C(R4a)xe2x80x94 by catalytic hydrogenation, using a suitable catalyst such as palladium-on-carbon in an appropiate inert or acidic solvent such as acetic acid. Where an optically active form of compounds of the formula (VI) is used in previous steps reduction of the  greater than Axe2x80x94Bxe2x80x94 double bond will produce diastereoisomers which may be separated. Where a particular diastercoisomer is of choice, a chiral asymmetry-inducing catalyst for the reduction can be used.
(h) The reaction between a compound containing T or T1 of the formula (IA) or (IB) wherein  greater than NR5 is  greater than NH (i.e. R5xe2x95x90H) and R10COL2, R10SO2L2 or R10CSL2 is conveniently carried out under similar conditions to those described for the acetylation or sulionylation of a compound of the formula (III)xe2x80x94see process (c).
(i) A compound of the formula (I) or (II) wherein R1 or R20 is azido may be prepared, for example, by reacting a compound of the formula (VIII) with sodium azide in an inert solvent such as DMF in a temperature range of ambient to 100xc2x0 C. normally in the region of 75xc2x0 C.-85xc2x0 C. A compound of the formula (VIII) may be prepared by converting the hydroxy group in a compound of the formula (I) or (II) wherein R1 or R20 is hydroxy into a tosyloxy or mesyloxy group by standard methods known in the art. For example, by reacting the compound of the formula (I) or (II) with tosyl chloride or mesyl chloride in the presence of a mild base such as triethylamine, or pyridine.
(j) A compound of the formula (I) or (II) wherein R1 or R20 is chloro may be prepared from a compound of the formula (VIII), by reacting the latter compound with lithium chloride and crown ether, in a suitable organic solvent such as THF, in a temperature range of ambient temperature to reflux. A compound of the formula (I) or (II) wherein R1 or R20 is (1-4C)alkylthio or (1-4C)alkoxy may be prepared by reacting the compound of the formula (VIII) with sodium thio(1-4C)alkoxide or sodium (1-4C)alkoxide respectively, in an alcohol or THF, in a temperature range of 0xc2x0 C. to reflux.
(k) The reaction of a compound of the formula (IX) with a nitrone of the formula benzyl-N(O)xe2x95x90CHxe2x80x94R6 in the presence of a Cu(I) salt (preferably CuCl), to give a compound of the formula (X) is performed in the presence of an amine complexing agent, such as triethylamine or pyridine, in a solvent such as pyridine or DMF, and at a temperature in the range 0xc2x0 C. to 80xc2x0 C. (preferably at or near ambient temperature). The subsequent reduction of the compound of the formula (X) may be performed using a mixture of LiAlH4 and aluminium chloride in an inert solvent such as THF, at a temperature in the range 0xc2x0 C. to 100xc2x0 C. (preferably at or near the reflux temperature of the solvent). Other reducing agents may also be used.
The compound of the formula (IX) may be prepared, for example, by introduction of the acetylenic group into a compound of the formula (IX) with a para-iodo group. See the specific Examples and J.Med.Chem. 1990, 33, 2574 for further details.
The nitrone of the formula benzyl-N(O)xe2x95x90CHxe2x80x94R6 may be prepared in-situ or separately from benzyl-NHOH and R6xe2x80x94CHO using chemistry well known in the art. Details concerning the processes (l), (m) and (n) are well known in the art. For process (l) an inert solvent (such as THF) and a temperature in the range 0xc2x0 C. to 100xc2x0 C. is preferred. For process (m) a low temperature is preferred. For process (n) a suitable halogenating reagent is PBr3 or PCl3, the reaction being performed preferably in an inert solvent such as chloroform or carbon tetrachloride and at a temperature in the range 0xc2x0 C. to 50xc2x0 C. (preferably at or near ambient temperature).
(o) When the R5 and R6 groups are linked to give a bicyclic ring structure for T or T1 (either before, or after, the coupling reaction between compounds of the formula (VII) and (VIIA) or (VIIB)), this may be achieved by, for example, dehydration (lactonisation) using, for example, a carbodiimide reagent in an inert solvent at a temperature in the range 0xc2x0 C. to 100xc2x0 C. (see for example, Example 10). A bicyclic ring system containing a urea functionality may be obtained, for example, from an amino-ester by reaction with a phenylisocyanate in the presence of a base (for example an alkoxide) in an inert solvent at a temperature in the range 0xc2x0 C. to 100xc2x0 C. (see for example. Examples 11 and 13). A bicyclic ring system containing an oxazolidinone ring may be obtained, for example, by carbonylation of an amino-alcohol using phosgene or carbonyl diimidazole (see, for example, Example 17).
When an optically active form of a compound of the formula (I) is required, it may be obtained by carrying out one of the above procedures using an optically active starting material, or by resolution of a racemic form of the compound or intermediate using a standard procedure.
Similarly, when a pure regioisomer of a compound of the formula (I) is required, it may be obtained by carrying out one of the above procedures using a pure regioisomer as an intermediate, or by resolution of a mixture of the regioisomers or intermediates using a standard procedure.
According to a further feature of the invention there is provided a compound of the formula (I), or a pharmaceutically-acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy.
According to a further feature of the present invention there is provided a method for producing an antibacterial effect in a warm blooded animal, such as man, in need of such treatment, which comprises administering to said animal an effective amount of a compound of the present invention, or a pharmaceutically-acceptable salt thereof.
The invention also provides a compound of the formula (I), or a pharmaceutically-acceptable salt thereof, for use as a medicament; and the use of a compound of the formula (I) of the present invention, or a pharmaceutically-acceptable salt thereof, in the manufacture of a novel medicament for use in the production of an antibacterial effect in a warm blooded animal, such as man.
In order to use a compound of the formula (I) or a pharmaceutically-acceptable salt thereof for the therapeutic treatment of mammals including humans, in particular in treating infection, it is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition.
Therefore in another aspect the present invention provides a pharmaceutical composition which comprises a compound of the formula (I) or a pharmaceutically-acceptable salt thereof and a pharmaceutically-acceptable diluent or carrier.
The pharmaceutical compositions of this invention may be administered in standard manner for the disease condition that it is desired to treat, for example by oral, rectal or parenteral administration. For these purposes the compounds of this invention may be formulated by means known in the art into the form of, for example, tablets, capsules, aqueous or oily solutions or suspensions, (lipid) emulsions, dispersible powders, suppositories, ointments, creams, drops and sterile injectable aqueous or oily solutions or suspensions.
In addition to the compounds of the present invention the pharmaceutical composition of this invention may also contain or be co-administered with one or more known drugs selected from other clinically useful antibacterial agents (for example xcex2-lactams or aminoglycosides). These may include penicillins, for example oxacillin or flucloxacillin and carbapenems, for example meropenem or imipenem, to broaden the therapeutic effectiveness against methicillin-resistant staphylococci. Compounds of this invention may also contain or be co-administered with bactericidal/permeability-increasing protein product (BPI) or efflux pump inhibitors to improve activity against gram negative bacteria and bacteria resistant to antimicrobial agents.
A suitable pharmaceutical composition of this invention is one suitable for oral administration in unit dosage form, for example a tablet or capsule which contains between 100 mg and 1 g of the compound of this invention.
In another aspect a pharmaceutical composition of the invention is one suitable for intravenous, subcutaneous or intramuscular injection.
Each patient may receive, for example, a daily intravenous, subcutaneous or intramuscular dose of 5 mgkg-1 to 20 mgkg-1 of the compound of this invention, the composition being administered 1 to 4 times per day. The intravenous, subcutaneous and intramuscular dose may be given by means of a bolus injection. Alternatively the intravenous dose may be given by continuous infusion over a period of time. Alternatively each patient will receive a daily oral dose which is approximately equivalent to the daily parenteral dose, the composition being administered 1 to 4 times per day.
Antibacterial Activity
The pharmaceutically-acceptable compounds of the present invention are useful antibacterial agents having a good spectrum of activity in vitro against standard Gram-positive organisms, which are used to screen for activity against pathogenic bacteria. Notably, the pharmaceutically-acceptable compounds of the present invention show activity against enterococci, pneumococci and methicillin resistant strains of S. aureus and coagulase negative staphylococci. The antibacterial spectrum and potency of a particular compound may be determined in a standard test system.
The antibacterial properties of the compounds of the invention may also be demonstrated in-vivo in conventional tests.
The following results were obtained on a standard in-vitro test system. The activity is described in terms of the minimum inhibitory concentration (MIC) determined by the agar-dilution technique with an inoculum size of 104 CFU/spot.
Staphylococci were tested on agar, using an inoculum of 104 CFU/spot and an incubation temperature of 37xc2x0 C. for 24 hours-standard test conditions for the expression of methicillin resistance.
Streptococci and enterococci were tested on agar supplemented with 5% defibrinated horse blood, an inoculum of 104 CFU/spot and an incubation temperature of 37xc2x0 C. in an atmosphere of 5% carbon dioxide for 48 hours-blood is required for the growth of some of the test organisms. Typically, compounds are active in the range 0.01 to 256 xcexcg/ml.
When tested, the compounds of the invention have MICs in the range 0.001 to 256 xcexcxcexcg/ml The following data were obtained for Example 44: